Genetics of Postpartum Depression in Affective Disorders

描述(由申请者提供)：这个职业发展奖励计划是一个五年计划，将使候选人发展成为一名独立的情感障碍遗传学研究员，重点是女性激素引发的症状。这位候选人是一名接受过情绪障碍培训的精神病学家，现在正在寻求进一步的遗传学和遗传流行病学培训。情感障碍遗传学研究小组主任、约翰霍普金斯大学精神病学系主任J.Raymond DePaulo博士将指导候选人在精神病人身上进行基因研究。约翰霍普金斯大学公共卫生学院教授特里·比蒂博士将指导候选人如何使用统计学方法和遗传流行病学。北卡罗来纳大学精神病学教授兼主席David Rubinow博士和生殖内分泌学研究部门负责人Peter Schmidt博士将指导候选人性激素对神经行为的影响以及女性心理健康的临床和表型问题。培训计划将通过一项研究计划得到加强，该计划基于一种假设，即患有产后抑郁症的女性在正常荷尔蒙变化时期具有遗传脆弱性，该变化包括对雌激素反应的基因(或多个基因)的变异。该研究计划将利用之前收集的双相情感障碍和反复发作的严重抑郁症的家庭样本。根据初步数据显示患有严重抑郁症和双相情感障碍的家庭对产后抑郁发作的熟悉程度，候选人将完成以下三个具体目标：1)完成对这一特征的连锁分析；2)进行关联研究，具体检查包含雌激素反应元件的感兴趣区域的基因，因此可能对产后期间发生的激素波动敏感；以及3)开始收集患有和不患有产后抑郁症的重度抑郁症女性的试点样本。这项拟议的研究具有重要意义，因为它将有助于更好地理解患有情绪障碍的女性产后抑郁的病理生理学，并可能有助于理解在女性群体中观察到的抑郁发作的增加。

DESCRIPTION (provided by applicant): This career development award proposal is a five-year plan that will enable the candidate to develop into an independent investigator in the genetics of affective disorders with an emphasis on hormonally-triggered symptoms in women. The candidate is an academic psychiatrist with training in mood disorders who now seeks further training in genetics and genetic epidemiology. Dr. J. Raymond DePaulo, Jr, director of the Affective Disorders Genetics Research Group and Chair of the Johns Hopkins Department of Psychiatry will mentor the candidate on conducting genetic research in the psychiatric patient. Dr. Terri Beaty, Professor at the Johns Hopkins School of Public Health, will mentor the candidate on using statistical methods and genetic epidemiology. Dr. David Rubinow, Professor and Chair of Psychiatry at the University of North Carolina and Dr. Peter Schmidt, Chief of the Unit on Reproductive Endocrinology Studies, will mentor the candidate in both the neurobehavioral effects of gonaldal steroids as well as clinical and phenotypic issues in women's mental health. The training program will be enhanced by a research plan based on the hypothesis that women with postpartum depressive episodes have a genetic vulnerability to times of normal hormonal change that consists of variation in a gene (or genes) that is estrogen responsive. The research plan will take advantage of previously collected family samples of bipolar disorder and recurrent major depression. Based on preliminary data demonstrating the familiality of postpartum depressive episodes in families with major depression and bipolar disorder, the candidate will complete the following three specific aims: 1) complete a linkage analysis for this trait; 2) perform association studies, specifically examining genes in regions of interest which contain estrogen-response elements and thus may be susceptible to the hormone fluctuations that occur during the postpartum period; and 3) begin collection of a pilot sample of women with major depression with and without postpartum depression. The proposed research is significant because it will lead to a better understanding of the pathophysiology of postpartum depression in women with mood disorders as well as potentially contribute to understanding the increased rate of depressive episodes observed in women as a group.